These studies are aimed at understanding the role of NK cells as a first line of defense against tumor cells and against virus infections. Studies are being performed with the mouse mutant beige, shown to be selectively devoid of NK activity. These mice were shown to resist transplantable tumors less well than control mice, as measured by transplantation assays and by short term elimination of radiolabeled i.v. injected tumor cells. They are now being analyzed for their resistance to spontaneous tumors and to primary tumor induction with DMBA and with MLV virus. We have also analyzed the possibility that NK cells may be of importance in regulating or eliminating certain primitive cell types from the organism. In support of this notion, NK cells can kill a subclass of immature cortical thymocytes, which occur mainly in very young mice of NK low reactive strains. Interferon was shown to play a major role in modulating levels of thymocyte sensitivity to NK lysis. Recently, these studies were extended to a human system, where human bone marrow, particularly when taken from fetuses, was found to be NK sensitive. We are now investigating if the colony forming granulocytic stem cells are among the cells killed by NK cells in human bone marrow.